| First Author | Shaposhnik Z | Year | 2007 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 27 |
| Issue | 3 | Pages | 621-7 |
| PubMed ID | 17158354 | Mgi Jnum | J:130538 |
| Mgi Id | MGI:3771888 | Doi | 10.1161/01.ATV.0000254673.55431.e6 |
| Citation | Shaposhnik Z, et al. (2007) Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions. Arterioscler Thromb Vasc Biol 27(3):621-7 |
| abstractText | OBJECTIVE: Recent evidence suggests that dendritic cells may play an important role in atherosclerosis. Based primarily on previous in vitro studies, we hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF)-deficient mice would have decreased dendritic cells in lesions. METHODS AND RESULTS: To test this, we characterized gene targeted GM-CSF(-/-) mice crossed to hypercholesterolemic low-density lipoprotein receptor null mice. Our results provide conclusive evidence that GM-CSF is a major regulator of dendritic cell formation in vivo. Aortic lesion sections in GM-CSF(-/-) low-density lipoprotein receptor null animals showed a dramatic 60% decrease in the content of dendritic cells as judged by CD11c staining but no change in the overall content of monocyte-derived cells. The GM-CSF-deficient mice exhibited a significant 20% to 50% decrease in the size of aortic lesions, depending on the location of the lesions. Other prominent changes in GM-CSF(-/-) mice were decreased lesional T cell content, decreased autoantibodies to oxidized lipids, and striking disruptions of the elastin fibers adjacent to the lesion. CONCLUSION: Given that GM-CSF is dramatically induced by oxidized lipids in endothelial cells, our data suggest that GM-CSF serves to regulate dendritic cell formation in lesions and that this, in turn, influences inflammation, plaque growth and possibly plaque stability. |
